The Caribbean sponge Batzella sp. contains a number of guanidine alkaloids, two of which, batzelladines A (1) and B (2), inhibit the binding of HIVgp-120 to CD4 and are therefore potential inhibitors of HIV. In addition to the known metabolites ptilomycalin A (6), ptilocaulin (7), crambescin A (8), crambescidin 800 (9), and crambescidin 816 (10), Batzella sp. contains five new alkaloids, batzelladines A-E (1-5), the structures of which were elucidated by interpretation of spectral data and chemical degradation.

Structure-directed screening identified the diphenyl lactone (1) as a specific inhibitor of the interaction of HIV gp120 with CD4. The compound bound selectively to gp120 in a time-dependent and irreversible fashion.

As part of a search for novel inhibitors of HIV-1 reverse transcriptase, the acetone extract of the giant African snail, Achatina fulica, was shown to be active. Fractionation of the extract yielded inophyllums A, B, C, and E and calophyllolide (1a, 2a, 3a, 3b, and 6), previously isolated from Calophyllum inophyllum Linn., a known source of nutrition for A. fulica. From a methanol/ methylene chloride extract of C. inophyllum, the same natural products in considerably greater yield were isolated in addition to a novel enantiomer of soulattrolide (4), inophyllum P (2b), and two other novel compounds, inophyllums G-1 (7) and G-2 (8). The absolute stereochemistry of inophyllum, A (1a) was determined to be 10(R), 11(S), 12(S) from a single-crystal X-ray analysis of its 4-bromobenzoate derivative, and the relative stereochemistries of the other inophyllums isolated from C. inophyllum were established by a comparison of their H-1 NMR NOE values and coupling constants to those of inophyllum A (1a). Inophyllums B and P (2a and 2b) inhibited HIV reverse transcriptase with IC50 values of 38 and 130 nM, respectively, and both were active against HIV-1 in cell culture (IC50 of 1.4 and 1.6 mu M). Closely related inophyllums A, C, D, and E, including calophyllic acids, were significantly less active or totally inactive, indicating certain structural requirements in the chromanol ring. Altogether, 11 compounds of the inophyllum class were isolated from C. inophyllum and are described together with the SAR of these novel anti-HIV compounds.